Imperial College London
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DrSilviaOttaviani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2823silvia.ottaviani

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stebbing:2020:10.15252/emmm.202012697,
author = {Stebbing, J and Krishnan, V and de, Bono S and Ottaviani, S and Casalini, G and Richardson, PJ and Monteil, V and Lauschke, VM and Mirazimi, A and Youhanna, S and Tan, Y-J and Baldanti, F and Sarasini, A and Terres, JAR and Nickoloff, BJ and Higgs, RE and Rocha, G and Byers, NL and Schlichting, DE and Nirula, A and Cardoso, A and Corbellino, M and Sacco, Baricitinib Study Group},
doi = {10.15252/emmm.202012697},
journal = {EMBO Molecular Medicine},
pages = {1--15},
title = {Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients},
url = {http://dx.doi.org/10.15252/emmm.202012697},
volume = {12},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI)-algorithms, to be useful for COVID-19 infection via a proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. Collectively, these data support further evaluation of the anti-cytokine and anti-viral activity of baricitinib and supports its assessment in randomized trials in hospitalized COVID-19 patients.
AU  - Stebbing,J
AU  - Krishnan,V
AU  - de,Bono S
AU  - Ottaviani,S
AU  - Casalini,G
AU  - Richardson,PJ
AU  - Monteil,V
AU  - Lauschke,VM
AU  - Mirazimi,A
AU  - Youhanna,S
AU  - Tan,Y-J
AU  - Baldanti,F
AU  - Sarasini,A
AU  - Terres,JAR
AU  - Nickoloff,BJ
AU  - Higgs,RE
AU  - Rocha,G
AU  - Byers,NL
AU  - Schlichting,DE
AU  - Nirula,A
AU  - Cardoso,A
AU  - Corbellino,M
AU  - Sacco,Baricitinib Study Group
DO  - 10.15252/emmm.202012697
EP  - 15
PY  - 2020///
SN  - 1757-4676
SP  - 1
TI  - Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients
T2  - EMBO Molecular Medicine
UR  - http://dx.doi.org/10.15252/emmm.202012697
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32473600
UR  - https://www.embopress.org/doi/abs/10.15252/emmm.202012697
UR  - http://hdl.handle.net/10044/1/80104
VL  - 12
ER  -
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